AZD vs. Opdivo - 1271750

politzer
Posts:6

Looking for some advice:

EGFR and T790M positive. 5th line treatment (Tarceva, Clovis, Chemo triplet, Afatinib). Started Nivolumab/Opdivo 3 weeks ago, had my second infusion this Wenesday. Simultaneously had my tissue sample from 2014 analyzed on the new Dako PD-L1 expression assay and it came back negative. Also simultaneously I'm preapproved for AZD9291 expanded access trial, which I could start in another 2 weeks. (Have to be off Nivolumab for two weeks).

I'm symptomatic with leptomenengial disease and new activity in the bowel, and have numerous small brain mets, although not symptomatic for those yet. No SE's yet on Opdivo.

My decision obviously is whether to continue on the current treatment, knowing (or thinking I know) that I don't have the target, or to jump to AZD, given that I do have the target. In just over two Nivolumab treatments, I'm not seeing any improvement in symptoms, rather the opposite. Fortunately the disease is, and has been, indolent. Hopefully it continues that way, but no guarantees.

I would appreciate real-life information on 1. success of Nivolumab without PD-L1, expression; 2. success of either drug in crossing the BBR, particularly regarding symptoms, and 3. information or advice on how long on Nivolumab before seeing results. I know this is asking a lot since the drugs are so new, and thanks in advance.

Cheers

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Reply # - November 7, 2015, 02:10 PM

catdander
Posts:

Hi politzer,

The short answer to is one immuno better than another is we don't know. It's too early in the immunotherapy game to say. However:

I've edited out a piece of info that doesn't make sense in this discussion...good to know we have the option of if in doubt ask a specialist.

Having said that, I'll ask one of our specialists to comment.

Best of luck,
Janine

Reply # - November 7, 2015, 06:31 PM

Dr West
Posts: 4735

Yes, you're right that most of these questions require more experience than has been described yet in the world. I can say that responses to osimertinib (AZD9291) have been reported after prior progression on rociletinib (CO-1686), including in the brain, but it's far too early to give numbers of what to expect.

The response rate to immunotherapy among patients with a driver mutation and acquired resistance is around 10%, perhaps a shade less. I can't say more than that responses in the brain have been reported -- too early to say how often or how effective.

About half of responses are seen by about 8 weeks, and about half are seen later, usually by 4 or 5 months. I would say that if someone is feeling worse rather than better after 2-3 infusions and there is an appealing alternative, it makes sense to favor the new option.

Good luck.

-Dr. West

Reply # - November 9, 2015, 09:48 AM

politzer
Posts: 6

Dr. West, thanks the insights, very helpful. One more question - do you have any insights into whether PD-L1 expression can change? The tissue sample that was assayed is from 2/2014 and I wonder if there would be any compelling reason to consider a new biopsy. The last one was problematic for pnuemothorax so I'm very leery, but it might be worth the risk. BTW, I was told that the Dako rep said my 2014 sample would be viable for testing.

Thanks again.

Reply # - November 9, 2015, 02:40 PM

catdander
Posts:

politzer, I've asked a specialist to comment on your new question. I very much hope you can put the brakes back on all this.

All the very best,
Janine

Reply # - November 9, 2015, 03:14 PM

Dr West
Posts: 4735

It's possible to see PD-L1 expression change from treatment or even just sampling a different area. I don't know that I would say I'd recommend a repeat biopsy or that a different result is likely, but it's certainly conceivable.

-Dr. West

Reply # - November 12, 2015, 11:23 AM

politzer
Posts: 6

Dr. West

I just saw your tweet on PD-L1 testing and responded. At this point, tissue sampling through biopsy is the only approved method of testing? And the Dako test is the only approved test for PD-L1?

It seems to me that, like severe mental health therapies, it's treat with immunotherapy and wait for the responses and diagnose from that.

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